Although it has been widely believed that MAbs would become important therapeutic agents, the use of MAbs to treat human disease has, with a few notable exceptions, met with considerable problems. A leading source of these problems has been the use of antibodies derived from mouse rather than human sources.While it has long been felt that human antibodies would be superior therapeutic agents, the generation of human MAbs has been problematic, in large part because a suitable fusion partner has not been generated. Such a fusion partner would yield stable clones with high antibody production following fusion and would not express its endogenous immunoglobulin genes.The goal of this proposed plan is to construct a superior fusion partner. The starting cell line has previously been demonstrated to give excellent fusion yields but secretes antibody prior to fusion.This line will be genetically engineered to disrupt its active immunoglobulin genes, thereby eliminating antibody production. The resulting fusion partner will provide the ability to develop commercially viable, clinically superior, human MAbs.